Persistent pain is a serious problem in premature, newborn and young infants. Although it is now known that neonates and young infants exhibit increased pain sensitivity, the fear that anesthetic agents produce respiratory depression, apnea and hypotension in newborns persists clinically and leads to an insufficient control of pain. Of importance for the future management of pain in newborns is the finding in rat pups and human infants that gustatory and orotactile stimulation access endogenous analgesic systems and lead to pain relieving and calming effects. The purpose of this project is to study the underlying mechanisms of gustatory stimulation-induced analgesia and anti-hyperalgesia. Our major hypotheses is that gustatory stimulation-induced analgesia and anti-hyperalgesia in rat pups is mediated, in part, via supraspinal descending pathways that modulate hyperexcitability at the level of the spinal dorsal horn. We will use a model of inflammatory hyperalgesia in rats because it mimics the persistent response to tissue injury produced by surgical intervention and traumatic injury in newborn humans. Correlative histochemical, pharmacological, molecular and physiological studies will be performed to determine the CNS mechanisms involved in the gustatory stimuli-produced behavioral analgesia and anti- hyperalgesia. Aim 1 will examine the postnatal time course of the effects of intraoral sucrose on paw withdrawal responses and test the hypothesis that these effects re mediated by brain stem descending pathways. Aim 2 will test the hypothesis that the behavioral analgesic and anti- hyperalgesic effects of intraoral sucrose involved opioid and monoaminergic mechanisms at the level of the spinal cord. Aim 3 will determine that sucrose-induced analgesia and anti-hyperalgesia suppress spinal dorsal horn neuronal activity and that this effect is produced by activation of descending modulatory systems. Aim 4 will determine the differential mechanisms by which intraoral sucrose modulates the response properties of dorsal horn neurons before and after inflammation. Aim 5 will extend the observations in Project #4 and test the hypothesis that gustatory stimulation in the newborn exposed to cutaneous and visceral inflammation projects against the development of altered nocifensive behaviors in the adult. These studies will lead to a better understanding of the development of analgesic mechanisms and will provide new clinical approaches for activating endogenous mechanisms in newborns.